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Glutamine suppresses dinitrophenol fluorobenzene-induced allergic contact dermatitis and itching: Inhibition of contact dermatitis by glutamine

  • Author Footnotes
    1 Z.W. Jin and H.-K. Kim equally contributed to this work.
    Zhe Wu Jin
    Footnotes
    1 Z.W. Jin and H.-K. Kim equally contributed to this work.
    Affiliations
    Institute of Hepato-Biliary and Pancreatic Surgery, Taishan Medical University, Shandong Province, Taiwan, ROC
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  • Author Footnotes
    1 Z.W. Jin and H.-K. Kim equally contributed to this work.
    Hae-Kyoung Kim
    Footnotes
    1 Z.W. Jin and H.-K. Kim equally contributed to this work.
    Affiliations
    Department of Immunology, Chonbuk National University Medical School, Jeonju, Chonbuk, Republic of Korea
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  • Chang-Hoon Lee
    Affiliations
    Department of Immunology, Chonbuk National University Medical School, Jeonju, Chonbuk, Republic of Korea
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  • Sung-Won Jung
    Affiliations
    Department of Plastic and Reconstructive Surgery, College of Medicine, Konyang University, Daejeon, Republic of Korea
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  • Sook-Jeong Shin
    Affiliations
    Biofoods Story, Inc., Seoshin-dong, Jeonju, Chonbuk 560-170, Republic of Korea
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  • Suhn-Young Im
    Affiliations
    Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Gwangju, Republic of Korea
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  • Author Footnotes
    2 B.-H. Cho and H.-K. Lee equally contributed to this work.
    Baik-Hwan Cho
    Footnotes
    2 B.-H. Cho and H.-K. Lee equally contributed to this work.
    Affiliations
    Department of Surgery and Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Chonbuk, Republic of Korea
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  • Author Footnotes
    2 B.-H. Cho and H.-K. Lee equally contributed to this work.
    Hern-Ku Lee
    Correspondence
    Corresponding author at: Department of Immunology, Chonbuk National University Medical School, 567 Baekje-daero, deokjin-gu, Jeonju-si, Jeollabuk-do 561-756, Republic of Korea. Tel.: +82 63 270 3069; fax: +82 63 250 4215.
    Footnotes
    2 B.-H. Cho and H.-K. Lee equally contributed to this work.
    Affiliations
    Department of Immunology, Chonbuk National University Medical School, Jeonju, Chonbuk, Republic of Korea
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  • Author Footnotes
    1 Z.W. Jin and H.-K. Kim equally contributed to this work.
    2 B.-H. Cho and H.-K. Lee equally contributed to this work.

      Abstract

      Background

      Cytoplasmic phospholipase A2 (cPLA2) is importantly implicated in a variety of inflammatory diseases by liberating arachidonic acid from phospholipids. The increased cPLA2 activities as well as increased levels of cPLA2 metabolites are associated with pathogenesis of many inflammatory skin disorders including atopic dermatitis. The non-essential amino acid l-glutamine (Gln) has been reported to have an anti-inflammatory activity. Regarding the molecular mechanism of Gln, we have recently shown that Gln effectively inhibits cPLA2 phosphorylation and activity.

      Objective

      To examine whether Gln could suppress allergic contact dermatitis (CD) induced on mouse ears by dinitrophenol fluorobenzene (DNFB).

      Methods

      Mice were sensitized five times on their ears with a 0.15% solution of DNFB in a 3 day interval. To examine Gln effects, Gln solution (4% in saline) was applied three times a day onto both sides of DNFB-applied ears from the last day of DNFB application. The inflammatory reactions of ears were evaluated by measuring ear thickness and hematoxylin and eosin (H&E) staining. Mouse scratching behavior was objectively evaluated using a MicroAct apparatus. cPLA2 phosphorylation and activity were analyzed using Western blotting and a cPLA2 assay kit, respectively.

      Results

      Topical application of Gln significantly attenuated inflammatory symptoms (ear thickness, histological inflammatory skin reactions) as well as itching. Gln inhibited cPLA2 phosphorylation and enzymatic activity. Arachidonyl trifluoromethyl ketone (AACOCF3) inhibited cPLA2 activity in DNFB-challenged ears and attenuated DNFB-induced ear inflammation and itching.

      Conclusion

      The results indicate that Gln suppresses DNFB-induced dermatitis and itching, at least in part, by inhibiting cPLA2 activity.

      Keywords

      Abbreviations:

      AACOCF3 (arachidonyl trifluoromethyl ketone), Ala (alanine), cPLA2 (cytosolic phospholipase A2), DNFB (dinitrophenol fluorobenzene), ESR (ear swelling response), Gln (l-glutamine), H&E (hematoxylin and eosin), 12-HPETE (12-hydroperoxyeicosatetraenoic acid), LT (leukotriene), PAR (proteinase-activated receptor), PMNL (polymorphonuclear leukocytes), siRNA (small interfering RNA), TRPV-1 (transient receptor potential vanilloid-type 1)
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